This application is from two experienced investigators who propose to utilize the newly developed technology of spermatogonial transplantation to answer fundamental questions in the field of male reproduction. The first two aims are to perform experiments which are a necessary prerequisite to eventual modification of the germ cell genome. We will utilize the vitamin A deficient rats and mice and prenatal and early postnatal mice as sources for undifferentiated spermatogonia for transplantation and cell culture. The spermatogonia will be transplanted into recipients of the same species (syngeneic-mouse to mouse or rat to rat) or another species (xenogeneic-rat to mouse or mouse to rat) before or after cell cultures. In the third aim, the analysis of the xenogeneic spermatogonial transplants will answer fundamental questions about the interactions between germ cells and Sertoli cells during spermatogenesis. For example, the cell type that controls the progression through or the timing of germ cell development can be determined after autoradiographic analysis of the xenogeneic transplants. The fourth aim involves experiments using testicular feminized or androgen insensitive strains of mice in transplantation experiments to answer long standing questions about the role of androgens in germ cell development. Overall, the transplantation model offers a new approach to answering questions about the fundamental control of spermatogenesis which have eluded investigators for many years. It also allows us to perform the initial steps necessary to modify the germ cell genome.